Thanks in part to the revolution cell therapy brought to treating blood cancers, the modality is now showing promise in some autoimmune applications. This expansion is poised to yield even wider benefits.
A decade ago, CAR T cell therapy rewrote the prognosis for blood cancers, delivering complete response rates greater than 50% in some indications. Now, drawing from lessons learned in oncology, CAR T is on the precipice of a therapeutic shift that may be even more consequential as drug developers expand its reach to the treatment of autoimmune conditions.
One clear and important example is the safety of these therapies. The severe cytokine release syndrome (CRS) that defined early CAR T experience in cancer has been substantially more manageable in autoimmune trials, not simply because the patients are healthier but because of lessons learned. Oncology research demonstrated that flooding a patient with more CAR T cells does not necessarily improve efficacy, but it does amplify toxicity. Building on this experience, autoimmune disease trials pair lower CAR T doses with aggressive early monitoring and prompt intervention to mitigate CRS severity.
In my role at the contract research organization Precision for Medicine, I work at the intersection of oncology and inflammatory disease, helping design and execute trials that depend on understanding which patients will respond and why. Based on the results I’ve seen, including in patients who previously had no effective treatment options, it’s clear to me that the expansion of CAR T into autoimmune diseases is the next chapter for a modality that started in oncology but may ultimately realize its full potential elsewhere.
Where CAR T works—and where it’s headed next
CD19-targeted CAR T works for blood cancers because it thoroughly depletes B cells, which display the CD19 protein. We expect that CAR T should also effectively treat autoimmune diseases such as lupus and multiple sclerosis (MS), where pathology stems from autoreactive B cells and the plasma cells they produce.
In cancer, the objective of CAR T is to kill tumor cells. In autoimmune diseases, the goal is more ambitious: immune reset. The hope is that deep B cell depletion may allow the immune system to reconstitute from naive precursors, inducing durable remission. Early data from lupus trials suggest this may happen. Whether it holds, and in whom, is the central question the field is working to answer.
As is typical with novel therapies, the patients entering these autoimmune trials are the most refractory, those who’ve exhausted conventional options without adequate disease control. CAR T is a serious intervention and the risk-benefit calculation is clearest in this population. But if CAR T demonstrates durable reset in patients with severe, refractory autoimmune disease, the results could support studying the modality as an earlier treatment option.
The resulting data may also inform efforts to move CAR T earlier in selected cancers.
Life-saving lessons
A fascinating question is how data generated in autoimmune diseases could change how CAR T is used in oncology.
Studies in lupus, inflammatory myositis and systemic sclerosis at Friedrich Alexander University, Erlangen-Nurnberg have demonstrated that a short, relatively tolerable preconditioning regimen was sufficient to support robust in vivo CAR T cell expansion and deep B cell depletion, followed by sustained, drug-free clinical responses. Because those responses persisted beyond CAR T cell disappearance and B cell reconstitution, the findings challenge the assumption that durable clinical benefit always requires prolonged cellular persistence. They also support investigation into whether lower-intensity conditioning could open the door to less toxic—or even outpatient—administration models in oncology.
Autoimmune trials are also incorporating biomarker strategies that could improve detection of early efficacy signals and enable faster dose optimization in oncology. These efforts build on the modular platform created in oncology where the antigen target, receptor design, cell source, dose and conditioning regimen can be adapted within a common framework. Autoimmune research is now extending that logic and expanding its value. Because the same pathogenic cell populations contribute to multiple autoimmune conditions, lessons about targets, dosing, conditioning and persistence can accumulate across indications even when the clinical presentation differs.
This cumulative learning could accelerate development and produce disease-specific therapies calibrated to achieve an immune reset with less toxicity and lower treatment burden. It may also feed back to oncology by showing when brief CAR T cell expansion or limited persistence is sufficient for effective treatment—in other words, that not every application requires the highest tolerable dose and longest possible persistence.
Tackling logistical and access challenges
Oncology has already shown that CAR T cannot be delivered by a single physician or department. Early programs had to coordinate hematology, cellular therapy, apheresis, pharmacy, neurology and critical care around one treatment. As monitoring and escalation protocols became standardized, more centers were able to deliver CAR T and select patients who could be treated in outpatient settings.
Autoimmune disease benefits from this coordination, while also adding a different and potentially more difficult form of collaboration involving shared clinical ownership across specialties. The cell therapy team understands lymphodepletion, product administration and acute toxicities. The rheumatologist or neurologist understands how to manage the underlying condition, interpret disease-specific symptoms and monitor for flares. Neither has all the expertise needed to manage the patient independently. Early CAR T trials for lupus and MS were conducted at large institutions with existing cell therapy infrastructure and where hematologists were accessible to their autoimmune colleagues. Scaling this beyond a handful of academic centers will require building that collaboration intentionally. That means active partnerships between hospitals with existing CAR T programs and rheumatology and neurology services, and a willingness among physician investigators to share patient care and ownership of a clinical trial protocol. The latter is perhaps harder than the science. However, the shared care models that develop could also benefit oncology by expanding treatment capacity and enhancing patient access through reduced burden.
Clinical coordination is only one part of the access challenge. Globally, there remains a mismatch between CAR T cell therapy innovation and implementation. In one U.S. claims analysis of commercially insured patients with B cell lymphoma, the median cost of the CAR T product alone was over $400,000. Access issues thus are a complex combination of sticker shock, convoluted reimbursement structures and localized logistical limits.
The autoimmune space has the potential to fundamentally change CAR T economics, thereby increasing access—for patients with those disease and for those with cancer.
Helping a patient with lupus or MS achieve sustained, drug-free remission eliminates decades of chronic immunosuppression, hospitalizations and downstream organ damage, lowering the long-term burden of care and providing justification for the upfront cost of CAR T. And it does so in a patient population that is often younger and potentially much larger than the oncology cohort. As autoimmune volumes grow and manufacturers respond with greater efficiency, the cost per treatment should decrease and modern payment models will emerge.
And this infrastructure, built to handle reimbursement and outcomes tracking at autoimmune scale, will support the delivery of these life-saving therapies in the oncology realm as well.
